Imipenem / Cilastatin — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	IV	5-10 mg/kg (based on imipenem component)	q6-8h	Duration: Varies; typically 5-14 days depending on infection severity Notes: Administer slowly over 30-60 minutes. Use with cilastatin (combination product). Adjust dose in renal impairment.
Cat	IV	5-10 mg/kg (based on imipenem component)	q6-8h	Duration: Varies; typically 5-14 days Notes: Administer slowly over 30-60 minutes. Use with cilastatin. Adjust dose in renal impairment.
Horse	IV	10-20 mg/kg (based on imipenem component)	q6h	Duration: Varies; typically 5-14 days Notes: Administer slowly over 30-60 minutes. Use with cilastatin. Monitor renal function.
Cattle	IV	10-20 mg/kg (based on imipenem component)	q6-8h	Duration: Varies; typically 5-14 days Notes: Extra-label use; not approved in food animals. Observe withdrawal times. Administer slowly.
Small Ruminants (sheep, goats)	IV	10-20 mg/kg (based on imipenem component)	q6-8h	Duration: Varies; typically 5-14 days Notes: Extra-label use; not approved in food animals. Observe withdrawal times. Administer slowly.
Rabbit	IV	10-20 mg/kg (based on imipenem component)	q6-8h	Duration: Varies; typically 5-14 days Notes: Extra-label use. Administer slowly. Monitor renal function.
Birds/Poultry	IV	10-20 mg/kg (based on imipenem component)	q6-8h	Duration: Varies; typically 5-14 days Notes: Extra-label use. Administer slowly. Not for use in laying hens if eggs for human consumption.
Exotic/Other	IV	10-20 mg/kg (based on imipenem component)	q6-8h	Duration: Varies; typically 5-14 days Notes: Extra-label use. Administer slowly. Monitor renal function.

Clinical Indications & Species Uses

General Indications

Treatment of serious infections caused by susceptible bacteria, particularly when other antibiotics have failed or are contraindicated

Dog (Canine)

Serious infections caused by susceptible bacteria, including multidrug-resistant infections (e.g., Pseudomonas, Enterobacter, Klebsiella, Acinetobacter)
Complicated urinary tract infections
Pyoderma with systemic involvement
Septicemia
Pneumonia
Intra-abdominal infections
Bone and joint infections

Cat (Feline)

Serious infections caused by susceptible bacteria, including multidrug-resistant infections
Complicated urinary tract infections
Septicemia
Pneumonia
Intra-abdominal infections

Horse (Equine)

Serious infections caused by susceptible bacteria, especially multidrug-resistant infections
Septic arthritis
Pneumonia
Peritonitis
Metritis
Wound infections

Cattle (Bovine)

Serious infections caused by susceptible bacteria, especially multidrug-resistant infections
Pneumonia
Metritis
Mastitis (systemic)
Septicemia

Small Ruminants (Sheep / Goat)

Serious infections caused by susceptible bacteria, especially multidrug-resistant infections
Pneumonia
Septicemia
Intra-abdominal infections

Rabbit & Small Mammals

Serious infections caused by susceptible bacteria, especially multidrug-resistant infections
Septicemia
Pneumonia
Abscesses (systemic)

Avian & Poultry

Serious infections caused by susceptible bacteria, especially multidrug-resistant infections
Septicemia
Pneumonia
Enteritis (systemic)

Exotic & Other Species

Serious infections in reptiles, small mammals, and other exotic species caused by susceptible bacteria, especially multidrug-resistant infections

Pharmacology & Mechanism of Action

Drug Class: Carbapenem antibiotic | Pharmacological Group: Beta-lactam antibiotic

Mechanism of Action: Imipenem is a carbapenem antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis and death. It is highly resistant to most beta-lactamases, including extended-spectrum beta-lactamases (ESBLs) and AmpC cephalosporinases, but can be hydrolyzed by carbapenemases. Cilastatin is a renal dehydropeptidase-1 inhibitor that prevents the renal metabolism of imipenem, thereby increasing its half-life and urinary concentration.

Pharmacodynamics: Imipenem is bactericidal and exhibits time-dependent killing. It has a broad spectrum of activity against many Gram-positive and Gram-negative aerobic and anaerobic bacteria, including Pseudomonas aeruginosa, Enterobacteriaceae, Bacteroides fragilis, and some Gram-positive cocci. It is generally inactive against methicillin-resistant staphylococci, Enterococcus faecium, and Stenotrophomonas maltophilia. The post-antibiotic effect is minimal for most organisms.

⚡ Pharmacokinetics Summary

Absorption: Imipenem is not absorbed orally and must be administered parenterally. After IV administration, it achieves high plasma concentrations rapidly.

Distribution: Imipenem distributes widely into tissues and fluids, including lung, kidney, bile, peritoneal fluid, and CSF (especially when meninges are inflamed). It crosses the placenta and is excreted in milk.

Metabolism: Imipenem is metabolized by renal dehydropeptidase-1 (DHP-1) in the proximal renal tubules. Cilastatin inhibits this enzyme, preventing metabolism and increasing urinary recovery of active drug.

Excretion: Imipenem and cilastatin are primarily excreted by the kidneys via glomerular filtration and tubular secretion. In humans, approximately 70% of imipenem is excreted unchanged in urine when given with cilastatin. In animals, similar renal excretion is expected.

Half-Life: In dogs: approximately 0.5-1 hour (with cilastatin). In horses: approximately 0.5-1 hour. In cattle: approximately 0.5-1 hour. Half-life may be prolonged in renal impairment.

Bioavailability: Not orally bioavailable; must be given IV or IM (IM only in some species, but not recommended in animals due to pain).

Protein Binding: Imipenem is approximately 20% protein-bound in humans; similar binding is expected in animals.

Available Formulations & Strengths

Injectable Solution (powder for reconstitution) 250 mg imipenem/250 mg cilastatin per vial; 500 mg imipenem/500 mg cilastatin per vial (IV)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to imipenem, cilastatin, or other beta-lactam antibiotics
Use in patients with a history of severe allergic reactions to penicillins or cephalosporins
Use in patients with severe renal impairment unless dose adjusted and monitored
Use in neonates or young animals with immature renal function unless absolutely necessary
Use in food animals is contraindicated due to lack of withdrawal times and potential for residues

Warnings & Clinical Precautions:

Use with caution in animals with a history of seizures or CNS disorders; imipenem can lower seizure threshold.
Use with caution in animals with renal impairment; dose adjustment is necessary.
Prolonged use may result in superinfection with resistant organisms (e.g., Candida, Pseudomonas).
Administer slowly IV to avoid nausea, vomiting, or hypotension.
Not for IM administration in animals due to severe pain and tissue irritation.
In food animals, extra-label use is prohibited in some countries; consult regulatory authorities.
Use only when culture and sensitivity indicate susceptibility, to preserve efficacy.

Adverse Effects & Reactions

Common:

Phlebitis at injection site
Nausea
Vomiting
Diarrhea
Hypersensitivity reactions (rash, fever)

Serious / Severe:

Seizures (especially with high doses or renal impairment)
Clostridium difficile-associated diarrhea
Anaphylaxis
Hepatotoxicity
Nephrotoxicity
Bone marrow suppression

Rare:

Pseudomembranous colitis
Eosinophilia
Thrombocytopenia
Stevens-Johnson syndrome

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Probenecid	Probenecid decreases renal tubular secretion of imipenem, increasing its plasma concentration and half-life.	Moderate
Ganciclovir	Concomitant use may increase risk of seizures.	High
Valproic acid	Imipenem may decrease valproic acid concentrations, leading to loss of seizure control.	High
Aminoglycosides	Additive nephrotoxicity and ototoxicity; monitor renal function.	Moderate
Loop diuretics (e.g., furosemide)	May increase risk of nephrotoxicity.	Moderate
Other beta-lactams	Potential antagonism; avoid concurrent use.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Seizures
Neurological signs (tremors, ataxia)
Nausea and vomiting
Renal impairment
Hypotension

Emergency Treatment Protocol: Discontinue drug immediately. Provide supportive care: maintain airway, breathing, and circulation. Administer anticonvulsants (e.g., diazepam) for seizures. Hemodialysis may be effective in removing imipenem and cilastatin in severe overdose. Monitor renal function and electrolytes. There is no specific antidote.

Food Animal Withdrawal Times

Not approved for use in food animals in many countries. If used extra-label, a prolonged withdrawal period (e.g., 30 days for meat, 7 days for milk) is recommended, but regulatory guidance should be consulted. In the US, extra-label use in food animals is prohibited if an approved drug exists that is effective and labeled for the condition.

Storage, Handling & Regulatory Information

Storage Temperature: Store powder at room temperature (20-25°C) before reconstitution. After reconstitution, the solution is stable for 4 hours at room temperature and 24 hours under refrigeration (2-8°C).

Handling & Special Conditions: Protect from freezing. Use within the specified time after reconstitution. Discard unused solution.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not approved for veterinary use in the US; human-labeled product used extra-label.

Extra-Label (Off-Label) Use: Extra-label use in animals is permitted under the Animal Medicinal Drug Use Clarification Act (AMDUCA) in the US, but only by or on the order of a veterinarian within a valid VCPR. Use in food animals requires extended withdrawal times and is prohibited if an approved drug is available. In the EU, similar rules apply under Regulation (EC) No 470/2009.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Imipenem/cilastatin is a potent carbapenem antibiotic reserved for serious, multidrug-resistant infections in veterinary patients. It should be used judiciously to minimize the development of resistance. Because it is a human-labeled drug, its use in animals is extra-label. It is administered intravenously, often in hospitalized patients. Doses are based on the imipenem component. Renal function should be monitored, and dose adjustments made in animals with renal impairment. Due to its broad spectrum, it is often used as a last-resort antibiotic. In food animals, its use is highly restricted due to lack of withdrawal data and public health concerns. Always perform culture and sensitivity testing before use. Monitor for adverse effects, especially seizures and gastrointestinal upset. Store and handle according to manufacturer instructions.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)